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The role of the nuclear hormone receptor RORγt in the development of lymph nodes and Peyer's patches

Authors

  • Gerard Eberl,

    Corresponding author
    1. Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, USA.
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  • Dan R. Littman

    1. Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, USA.
    2. Howard Hughes Medical Institute, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY, USA.
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Gerard Eberl
Molecular Pathogenesis Program
Skirball Institute of Biomolecular Medicine
New York University School of Medicine
540, First Avenue
New York, NY 10016
USA
Tel.: +1 212 2636921
Fax: +1 212 2631498
E-mail: eberl@saturn.med.nyu.edu

Abstract

Summary:  The nuclear hormone receptor retinoic acid-related orphan receptor (ROR)γt is required for the development of lymph nodes (LNs) and Peyer's patches (PPs), as these organs are absent in RORγt-deficient mice. During fetal life, RORγt is expressed exclusively in lymphoid tissue-inducer (LTi) cells, a cell type that localizes in developing LNs and PPs. LTi cells express surface lymphotoxin α1β2 that activates specialized mesenchymal cells to produce chemokines, upregulate adhesion molecules and induce further maturation of lymphoid organs. RORγt inhibits nuclear factor of activated T-cell (NFAT) function in cell lines and induces the expression of Bcl-xL and p27kip1 in the adult thymus, suggesting that RORγt prevents cell activation, cell-cycle progression, and apoptosis. We propose that RORγt, together with the inhibitor of basic helix-loop-helix transcription factor Id2, ensures generation and survival of fetal LTi cells necessary for the development of LNs and PPs.

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